Novel Function of Isoamylamine Improves Survival in Endotoxemic Mice by Ameliorating Coagulopathy and Attenuating MMP-9 Expression Through p-ERK/p-p38 Signaling at Early Stage

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Abstract

When a host suffers endotoxemic shock or septic shock, it results in many symptoms including disseminated intravascular coagulation (DIC). Septic shock (SS) causes coagulation time to decrease and then gradually increase, finally becoming prolonged and giving rise to DIC. Isoamylamine (IA) is one of the main components of grape products and can improve the survival rate of endotoxin lipopolysaccharide (LPS)-induced endotoxemic shock. The aim of this study was to elucidate if IA ameliorates coagulopathy in the early phase of LPS-induced damage. We studied the effects of IA on the coagulation system of extrinsic (prothrombin time [PT]) and intrinsic (activated partial thromboplastin time [aPTT]) pathways. PT and aPTT were tested in plasma drawn from mice following intraperitoneal (IP) injection of 1 mL of 1,000 ppm IA after LPS administration. Shortened PT was ameliorated by 1,000 ppm IA 1 h after LPS administration, but there was no effect on aPTT. In conclusion, IA 1,000 ppm partially intervenes in the early phase of LPS-induced damage, shortening plasma PT 1 h after LPS treatment in mice. Furthermore, we found 1,000 ppm IA also could attenuate MMP-9 expression through p-ERK/p-p38 signaling in mice hepatocyte extracts. This study focused on the effects of IA on blood coagulation function and inflammatory proteins. In the current situation of absence of effective treatment for SS, IA can increase survival rate and may offer another choice of patient avoiding causing death during endotoxemic shock.

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